晚期甲状腺癌靶向药物不良反应管理专家共识（2023年版）

doi:10.19401/j.cnki.1007-3639.2023.09.009

摘要/Abstract

摘要：

近年来，靶向治疗已成为晚期甲状腺癌的标准治疗方法。虽然中国临床肿瘤学会甲状腺癌专家委员会在2018年出版了针对放射性碘难治性分化型甲状腺癌（radioactive iodine-refractory differentiated thyroid cancer，RAIR-DTC）的靶向药物不良反应专家共识，但目前靶向治疗获批的类型已延伸至甲状腺髓样癌（medullary thyroid cancer，MTC）和甲状腺未分化癌（anaplastic thyroid cancer，ATC），靶向药物也从多靶点激酶抑制剂（multikinase inhibitors，MKIs）延伸至BRAF抑制剂、MEK抑制剂、RET抑制剂和TRK抑制剂。随着多种不同作用机制的靶向药物在临床上的广泛应用，并且考虑到众多来自不同科室的医师涉及晚期甲状腺癌的靶向治疗，靶向药物的不良反应管理急需不断规范和完善。因此，中国临床肿瘤学会甲状腺癌专家委员会组织专家组进行深入探讨，共同制定了本专家共识，旨在形成相对规范统一的认识，更好地指导临床实践。

关键词: 晚期甲状腺癌, 靶向药物, 不良反应, 专家共识

Abstract:

Recently, targeted therapy has become the standard of care for advanced thyroid cancer. Although expert consensus on the management of adverse events in patients receiving targeted agents for radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) was formulated by Thyroid Cancer Committee of Chinese Society of Clinical Oncology in 2018, the tumor types which are eligible for targeted therapy have been extended to medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), and targeted agents have been approved from multikinase inhibitors (MKIs) to BRAF inhibitors, MEK inhibitors, RET inhibitors and TRK inhibitors. Along with the widely used targeted agents with different mechanism, the management of adverse events for targeted agents needs to be standardized and improved, especially considering the specialties of the physicians who are involved in the targeted therapy for thyroid cancer are variable. Therefore, Thyroid Cancer Committee of Chinese Society of Clinical Oncology convened an expert task force charged with developing consensus to serves as a guidance to standardize utilization of targeted agents and to optimize clinical practice.

Key words: Advanced thyroid cancer, Targeted agents, Adverse events, Expert consensus

中图分类号:

R736.1

薛丽琼, 郭晔, 陈立波. 晚期甲状腺癌靶向药物不良反应管理专家共识（2023年版）[J]. 中国癌症杂志, 2023, 33(9): 879-888.

XUE Liqiong, GUO Ye, CHEN Libo. Expert consensus on the management of adverse events in patients receiving targeted agents for advanced thyroid cancer (2023 edition)[J]. China Oncology, 2023, 33(9): 879-888.

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项目	索拉非尼^[7]（n = 207）	仑伐替尼^[8]（n = 103）	多纳非尼^[9]（n = 128）	安罗替尼^[11]（n = 62）
3/4级不良反应	64.3	87.4	43.8	58.1
严重不良反应	37.2	38.8	7.8	12.9
剂量下调	64.3	80.6	42.2	32.3
治疗暂停	66.2	67.0	42.2	NR
治疗终止	18.8	8.7	6.3	16.1

不良反应	索拉非尼^[7]（n = 207）		仑伐替尼^[8]（n = 103）		多纳非尼^[9]（n = 128）		安罗替尼^[10-11]（n = 138）
不良反应	任意级别	≥3级	任意级别	≥3级	任意级别	≥3级	任意级别	≥3级
HFSR	76.3	20.3	58.3	9.7	84.4	12.5	68.8	16.7
高血压	40.6	9.7	81.6	62.1	46.9	13.3	67.4	28.9
腹泻	68.6	5.8	49.5	6.8	63.3	3.1	42.7	6.5
蛋白尿	NR	NR	80.6	23.3	38.3	1.6	63.0	2.9
体重下降	46.9	5.8	47.6	2.9	34.4	1.6	26.1	5.1
食欲下降	31.9	2.4	20.4	1.9	14.8	0.8	30.4	0.7
谷丙转氨酶升高	12.6	2.9	NR	NR	14.1	1.6	35.5	0.7
谷草转氨酶升高	11.1	1.0	NR	NR	10.9	0.8	28.3	0.7
低钙血症	18.8	9.2	29.1	3.9	22.7	3.1	NR	NR

项目	ATC^[15]（n= 36）	RAIR-DTC^[16]（n= 27）
3/4级不良反应	58	48
严重不良反应	19	NR
剂量下降	47	56
治疗暂停	50	NR
治疗终止	17	22

不良反应	普拉替尼^[17]（n = 28）		赛普替尼^[18]（n = 77，其中30例为甲状腺癌）
不良反应	任意级别	≥3级	任意级别	≥3级
高磷血症	57.1	0.0	NR	NR
白细胞减少	57.1	14.3	31.2	3.9
中性粒细胞减少	53.6	28.6	24.7	3.9
谷草转氨酶水平升高	53.6	0.0	61.0	15.6
乳酸脱氢酶水平升高	50.0	0.0	20.8	0.0
肌酸激酶水平升高	46.4	21.4	NR	NR
谷丙转氨酶水平升高	42.9	3.6	62.3	15.6
低钙血症	39.3	10.7	NR	NR
胆红素升高	NR	NR	39.0	0.0
血小板减少	NR	NR	37.7	10.4
贫血	35.7	10.7	NR	NR
高血压	25.0	10.7	33.8	15.6
低白蛋白血症	28.6	0.0	26.0	1.3
腹泻	NR	NR	28.6	1.3
血肌酐水平升高	25.0	0.0	23.4	0.0
高尿酸血症	NR	NR	20.8	0.0

不良反应	拉罗替尼^[19]（n = 30）		恩曲替尼^[21]（n = 68，其中5例为甲状腺癌）
不良反应	任意级别	≥3级	任意级别	≥3级
疲劳	26.7	0	35	7
头晕	26.7	0	26	2
谷草转氨酶水平升高	26.7	0	12	2
谷丙转氨酶水平升高	26.7	0	11	2
肌肉痛	26.7	0	12	0
味觉障碍	NR	NR	47	0
便秘	16.7	0	28	0
腹泻	10.0	0	29	2
外周水肿	13.3	0	26	2